One of the goals of this proposed work is to isolate from rabbit and mouse thymus a factor (LPIF) which inhibits the in vitro phytohemagglutinin-stimulated proliferation of lymphocytes. The production of LPIF by cells of thymus, bone marrow and spleen of mouse, rabbit, calf and pig has been recently shown in the laboratory of the applicant. It is also proposed to study a possible immunosuppressive role of LPIF in the regulation of the immunological response. Experiments directed at exploring the mechanism of the in vitro inhibitory action of LPIF will also be carried out. It has been shown in the laboratory of the principal investigator that thymus, bone marrow and spleen cells of AKR mice do not produce LPIF. In this grant application we propose to study the possible relevance of this impairment of the production of LPIF to the pathogenesis of AKR mice leukemia. We also plan to carry out a study of LPIF in NZB mice. Due to the fact that the thymus gland seems to be involved in the pathogenesis of the autoimmune hemolytic anemia of NZB mice, it is possible that a deficient production of LPIF may play a causative role in this disease. The study of LPIF in the hemolytic anemia of NZB mice is justified also by the well known relationships existing between autoimmune diseases and malignancies of the reticulo-endothelial system, both in humans and mice. All the standard biochemical techniques, and most of the immunological techniques that will be used for the isolation of LPIF are operational in the laboratory of the principal investigator. BIBLIOGRAPHIC REFERENCES: G. Di Sabato, D. M. Chen, and J. W. Erikson, Production by Murine Spleen Cells of an Activity Stimulating the PHA- Responsiveness of Thymus Lymphocytes. Cell. Immunol. 17, 495-504 (1975). D.-M. Chen and G. Di Sabato, Further Studies on the Thymocyte Stimulating Factor. Cell. Immunol. 22: 211 (1976),